November 28, 2023

Trial results showing that a potent anti-obesity drug offers strong protection against serious heart problems have electrified researchers. They say that the findings could change how this and other members of a new generation of obesity drugs are used, and who receives them.

The full data from the trial of Wegovy — a trade name for the drug semaglutide — have not yet been made public. But results announced by manufacturer Novo Nordisk, headquartered in Bagsværd, Denmark, show that a weekly dose of Wegovy slashed the risk of severe cardiovascular events by 20% in adults with heart disease and either overweight or obesity. The results are the first to suggest that semaglutide protects against serious episodes of cardiovascular disease in people who do not have type 2 diabetes.

Researchers say the findings, if confirmed, could change the practice of preventive cardiology. The results also suggest that the new generation of anti-obesity drugs can profoundly improve health, not just reduce weight. “This is probably the most important study in my field in the last ten years,” says Michael Blaha, director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, Maryland. ”It gets to that cardiometabolic risk that’s been difficult to treat in practice.”

”It’s hard to think of other [drugs], apart from statins, that have shown such a profound effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, California.

When will the full details be released?

The trial’s full results are expected to be presented at a conference later this year. What’s known so far is that the study, named SELECT, enrolled 17,604 people who already had cardiovascular disease, but no history of diabetes. Participants received injections of either Wegovy or a placebo, and were followed for up to five years. Those who got the drug had a lower risk of heart attack, stroke and death from cardiovascular disease than those who received the placebo.

What’s driving the risk reduction?

Semaglutide, which is sold under the names Wegovy for obesity and Ozempic for diabetes, acts by mimicking a hormone called glucagon-like peptide 1 (GLP-1), which is associated with appetite regulation.

Researchers expected Wegovy to protect against heart disease. Obesity itself is an important risk factor for cardiovascular disease, and weight loss can lead to improvements in other risk factors such as blood pressure and cholesterol levels. But changes in factors other than these might contribute to cutting risk. There’s evidence that drugs that mimic GLP-1 can improve fatty-acid metabolism and reduce inflammation, for example, says Gulati. “This is what’s so fascinating about these drugs. They work on the brain, the pancreas, the cardiovascular system, the gastrointestinal tract … There’s more to them than simply weight loss.”

More data could help to explain whether the protective effect is associated mostly with weight loss or is triggered by other changes promoted by the drug.

Could the new obesity drugs prevent other diseases?

Because obesity is tied to conditions such as hypertension, sleep apnoea and nonalcoholic fatty liver disease, “it is likely that by reducing weight, these comorbid disease conditions will also improve”, says Joseph Wu, the president of the American Heart Association and a cardiologist at the Stanford University School of Medicine in California.

Blaha notes that the SELECT trial examines a narrow set of severe cardiovascular events and probably underestimates semaglutide’s benefits for cardiovascular health and its potential to enhance mobility, mood and other traits that tend to improve in people who experience weight loss.

Will the results change how physicians prescribe the drug?

Medications such as Wegovy will probably be embraced by a wider range of providers, not only obesity specialists, says Beverly Tchang, an endocrinologist at Weill Cornell Medicine in New York City. She says the results reinforce that Wegovy is a cardiovascular medication as well as a weight-loss drug.

Wu agrees. “We will likely see an increase of the drug being prescribed to overweight patients with cardiovascular risk factors,” he says.

The reframing of Wegovy as a medication for cardiovascular conditions, as opposed to one for obesity, might also improve its acceptability as a long-term drug. “As a cardiology medication, people will take it more seriously,” Tchang predicts.

Novo Nordisk expects to apply for approval for more conditions to be treated using Wegovy, both in the United States and in Europe, by the end of the year. The full trial results should provide sufficient evidence for the US Food and Drug Administration to approve the drug for cardiovascular-risk reduction, according to specialists. “With that label change, I think we’re going to see an even greater prescription of this drug,” Blaha says.

Cardiologists hope that the SELECT trial’s results will help the drug to become more widely accessible. Some US insurance companies cover the cost of the medication only for people with diabetes. Physicians want to use the new GLP-1-mimicking drugs but hesitate out of fear of “giving hope to our patients, only [for them] to be turned down by their insurance,” Gulati says. Broader insurance coverage “will be a game -changer for the clinical practice of preventive cardiology.”

This article is reproduced with permission and was first published on August 10, 2023.


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